Note: Descriptions are shown in the official language in which they were submitted.
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TITLE: SENSOR DEVICES AND ANALYTICAL METHOD.
This invention relates to sensor devices and more
particularly to electrochemical sensor devices, and to
analytical methods using them.
various types of electrodes are known for use in the
electrochemical analysis of samples, and one of these is
the ion-selective electrode (conveniently referred to as an
"ISE"), which functions on the basis of measuring the
electrical potential of the ISE when in contact with the
sample. This requires two electrodes - one being the ion-
selective electrode ( ISE) and the other being a reference
electrode assembly. Such electrodes are well-known. The
reference electrode assembly usually employs a liquid
junction between (a) the sample and (b) the reference
electrode and its associated internal electrolyte. The
liquid junction maintains electrical continuity in the
electrochemical cell while restricting contamination of the
inner electrolyte of the reference electrode assembly by
the sample.
Other potentiometric measurements are made based on
redox reactions at electrodes, preferably metals such as
platinum and gold. A reference electrode is required for
these measurements, and both the redox and the reference
electrode assemblies should contact the sample.
The known methods and devices for using detecting
electrodes such as an ISE or redox electrode for detection
and/or measurement purposes are all based on the simple
procedure of putting both the detecting electrode and the
liquid junction of the reference electrode assembly in
contact with the sample, and then measuring the electrical
potential between the detecting electrode and the reference
electrode. Appropriate analytical conclusions are drawn
from the measurements of this potential, e.g. by comparison
with the potential generated when standard solutions are
used.
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However, the known devices and systems have been found
to suffer from disadvantages so that they are not entirely
satisfactory in use, because the standard modes for using
them require careful calibration against standards and also
stabilisation before they can give accurate or reliable
results.
Proposals have been made for various forms of active
electrode which are covered or surrounded by a membrane, as
a feature which can serve to protect the electrode from
physical damage or, more commonly, to retain a controlled
internal electrolyte or liquid film or to confer other
selective control over how the different components from a
sample can gain access to the electrode. Such control is
often needed when a sample under examination contains
compounds which can interfere seriously With the detection
of desired analytes at the electrode - sometimes by
behaving similarly to the analyte and sometimes by de-
activating (fouling) the electrode so that it ceases to
function properly.
This selectivity can act in several Ways, but with the
aim of holding back an undesirable interfering component
while the desired analyte can pass on towards the detecting
electrode. This can be simply by molecular size or
molecular charge (polarity), but an alternative way is to
incorporate into the membrane a reactive component which
may either destroy the undesirable interferenta or convert
the desired component into another compound which is more
readily able to reach the electrode and be determined
there. An example is an enzyme electrode, particularly one
3d in which glucose oxidase is used to catalyse the oxidation
of glucose to form by-product hydrogen peroxide which
readily passes on to the electrode.
Despite their merits for some purposes, membrane
barriers are regarded as a necessary nuisance that slows up
responses When rapid response and equilibrium are wanted.
As most active sensing electrodes are used in
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amperometric mode for detection and measuring analyte
contents of samples, the conventional procedure of plotting
measurements of current flow approaches zero (or at least
very small current values) and this level (a «baseline~~)
can be used for reference or as a starting point for making
measurements of the analyte content. In contrast to this,
ISEs operate in a very different way, as they generate the
voltage to be measured and normally respond within
milliseconds to seconds, and the desired baseline can be
almost anywhere in terms of any measurable mV values.
Therefore satisfactory measurements with such electrodes
can be made very difficult by this phenomenon, termed
~~baseline drift . ~~
We have found that these problems can be overcome by
using a membrane which is not selective in favour of a
desired analyte, and may even slow up access of the desired
analyte to the electrode. This is novel and in contrast to
the known methods of using membranes, where the membrane is
acts in the opposite manner and is used to impede the
access of undesirable interferents without impeding the
access of desired analyte. Especially, we have found that
a sensor system using a permeable barrier (e. g. a membrane)
in this novel Way can enable an analyte to be determined
very much more readily, by measuring the rate of change of
output signal from the detecting electrode, which is caused
by the regulated diffusion of the analyte through the
membrane. Plotting the output signal from the ISE against
time gives a measure of this rate generates a graph in
which the slope determines the measured parameter. Any
slowness in the response is no longer a nuisance, so long
as the electrode system and measuring equipment can discern
this rate of change, usually as the slope of the response
chart or graph, and more reproducible readings can be
obtained by ensuring that the membrane transport (the rate
of passage of the analyte through the membrane) is the
detexmining factor for the procedure.
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In our knowledge and experience, IS$s in particular
have so far been used only in bare form, without a covering
membrane, so the covering technique is new - especially for
an ISB and, we believe, for other detecting electrodes too.
It offers the further advantages that the signal from the
electrode may not need to fully reach equilibrium, and of
being applicable to any other electrode which functions in
a non-amperometric manner.
So, we have now found that the difficulties can be
overcome by covering the detecting electrode with a
permeable barrier of restricted permeability which then
interfaces with the sample, so that the sample itself no
longer provides the sole bridging contact between the
detecting electrode and reference electrode assembly to
complete the measuring circuit. This permeable barrier
allows the system to operate by diffusion of components,
between the sample and the region within the permeable
barrier, before the output signals from the electrodes are
measured and such measurements are used as a basis for the
determination of the composition of the sample. For this,
the permeable barrier covers at least the detecting
electrode, and preferably both the detecting electrode and
the reference electrode assembly.
Thus according to our invention we provide a sensor
system comprising a detecting electrode and a reference
electrode in combination, characterised in that the
detecting electrode is enclosed within a permeable barrier
adapted to interface with a sample under examination, so
that the sample itself no longer provides the main bridging
contact between the detecting and reference electrodes to
complete the measuring circuit.
Preferably, both the detecting electrode and the
reference electrode are enclosed within the same permeable
barrier to separate them from the sample.
Thus according to our invention we also provide a
sensor device comprising a detecting electrode and a
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reference electrode in combination, characterised in that
these are both enclosed within a permeable barrier adapted
to interface with a sample under examination, so that the
sample itself no longer provides the main bridging contact
between the detecting electrode and the reference electrode
to complete the measuring circuit.
Our invention also provides an improved method for the
determination of an analyte in a sample, which comprises
using a sensor device with an ion-selective electrode or
redox electrode and a reference electrode assembly in
combination as described herein.
Thus according to our invention we also provide a
method for the determination of an analyte in a sample,
which comprises using a sensor system or device with a
detecting electrode and a reference electrode in
combination, characterised in that the detecting electrode
(and preferably also the reference electrode) is enclosed
within a permeable barrier adapted to interface with a
sample under examination, so that the sample itself no
longer provides the main bridging contact between the
detecting and reference electrodes to complete the
measuring circuit, measuring the potential between the
detecting electrode and the reference electrode and using
this measure for determining the content of the analyte.
An arrangement in which the pern~eable barrier encloses
the detecting electrode, together with the reference
electrode, is advantageous in use and gives better results.
The two types of electrode used (the detecting
electrode and the reference electrode) are well-known and
are amply described in the literature. Their precise form
and construction are not critical but the following summary
assists in describing them.
The reference electrode may be any of those known or
used in the art. The preferred and most convenient form of
reference electrode assembly comprises a conventional half
cell containing a silver/silver chloride (Ag/AgCl) or
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calomel electrode system, with its conventional filling
solution (usually an electrolyte), enclosed in a container
which has a "liquid junction", "salt bridge" or "double
junction" arrangement customarily intended to make contact
5 with the sample. This "liquid junction" is commonly a
porous membrane which serves to allow the necessary
electrical conductivity to complete the electrical
measuring circuit while restricting flow and/or diffusion
of the sample or its components into the reference cell or
10 any outward flow to contaminate the sale. The presence
of a further permeable barrier between the reference
electrode and the sample, as in the present invention, also
provides a further safeguard against such contamination.
For ease of fabrication, forms having simple geometry,
15 for example planar forms, are most convenient.
Construction may also be simple. For example, a Ag/AgCl
electrode may be overlaid with a membrane of material such
as polyvinyl alcohol, which readily hydrates and (in terms
of the electrode potential) the arrangement is
20 satisfactorily stable, especially when the electrode is
required for only a short measurement duration.
The detecting electrode for use in our invention may
be any of those known or used in the art for detecting
analytes by producing output signals representative of a
25 component or characteristic which can provide a measure of
the analyte present in a sample under examination.
The preferred detecting electrode is one which is not
normally used in an amperometric measuring mode, and the
signal output (potential) is preferably measured by a non
30 amperometric method.
Especially, it may be an ion-selective electrode
("ISE") for example a conventional ion-selective electrode
with an internal electrolyte and an internal reference
(e. g. Ag/AgCl) or a coated wire electrode where a base
35 metal wire is in direct contact with a covering ion-
selective membrane. The invention is applicable to a
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variety of alternative forms of detecting electrode, for
example redox electrodes, and is not limited only to use
for ISE devices.
In this specification the term "ion-selective" has
5 been used, but it should be noted that in the art the term
"ion-sensitive" is also used, and these two terms are to be
regarded as interchangable for the purposes of this
invention.
The ISE response is a potential change across a
10 membrane or coating, and the IS8 assembly includes this
layer and an internal electrode, covered or enclosed by the
coating or membrane material having the ion-sensitive or
ion-selective properties. This coating or membrane surface
interacts with the ionic components from a sample to
15 generate a measuring voltage (EMF) and may allow
preferential interaction or passage of those ions which it
is desired to measure. the internal electrode may be a
conventional one capable of use for measurement of
electrochemical potentials such as Ag/AgCl but may also be,
20 for example, metals such as platinum, gold, silver or
copper (though others may be used if desired) as in coated
wire electrodes. Examples of coatings include those
containing additive components which are ion-selective in
the sense of having powers for ion-exchange, ion-
25 adsorption, complex-forming neutral compounds or chelating
ions, or the like, or combinations of such properties.
Examples include liquid ion exchangers, neutral carriers
and plasticisers (solvents) retained physically or
incorporated into a polymer layer in any combination or
30 singly. The potential forms at the coating or membrane, or
across it; the internal electrode is there simply to make
a contact and, like the reference electrode, to be used to
measure potential between two points either side of the
membrane.
35 Likewise, solid-state electrodes may be used without
the need for an ion-selective coating if they already
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themselves possess the necessary ion-selective properties.
The ISE usually comprises a covering or layer (e.g. a
membrane or a gel) over an internal core sensing electrode
and the components imparting ion-sensitivity may be in or
on the internal core sensing electrode and/or the said
covering or layer. A common form of ISE may contain, when
in use, an inner medium (commonly an electrolyte), which
may conveniently be in liquid or gel form, and associated
contacting electrodes. The inner medium is usually aqueous
but may be non-aqueous if desired, or contain a combination
of aqueous and non-aqueous components.
Alternatively, it may be a solid-state electrode, for
example any of those available commercially. One form of
these can be used to detect chloride ions (Cl-). Examples
of this type include ion-selective field effect transistors
(conveniently referred to as °ISFET" devices).
The detecting electrode (e.g. ISE) can be in any
convenient shape. It is easy and convenient to make them
in planar form, for example as a flat form of the coated
wire.
It is possible also for the reference electrode to be
another ISE which is under conditions which make it produce
a stable EMF, in a manner comparable to a true conventional
reference electrode. This can, if desired, be another ISE
with an inner (and constant) stable electrolyte within the
porous liquid-junction membrane.
The permeable barrier surrounding the detecting
electrode - or the detecting electrode and reference
electrode - may be of various materials and forms. Its
main function is to enclose the detecting electrode (or the
detecting electrode and reference electrode assembly) and
providing the means for contact with the sample, but also
it may serve to hold the two electrode systems together as
a single assembly, and even provide some protection for
them against damage from contact with other bodies. Also,
it usually contains a zone of liquid (e. g. electrolyte)
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medium enclosed within the permeable barrier. As the main
function of the permeable barrier is to slow the rate of
diffusion of analyte, it is preferably is not selective in
favour of the analyte sought.
The permeable barrier may be made of any material
which can provide the desired degree of permeability
towards the sample or its components in addition to a
sufficient degree of cohesion, strength and durability to
maintain its physical integrity while the device is in
contact with the sample and in use.
Conveniently, it may be simply a membrane or a gel,
but it may comprise any combination of these - using one or
more of either type of material (which may be the same or
different) if desired. As its principal purpose is only to
regulate, by diffusion, access of the sample or its
components to the detecting electrode and the reference
electrode assembly, its composition and form are not
critically important. The range of suitable materials is
therefore quite conveniently extensive, (and can be used to
improve selectivity), Which is one of the advantages of our
invention. Also, when the detecting electrode (e. g. ise)
and the reference electrode are both under the cover of the
permeable barrier, it does not matter whether or not the
barrier may produce a potential of its own (e.g. a
~~membrane potential") because such a potential, if
generated, does not alter the potential difference which we
wish to use -- i.e. the potential between the detecting
electrode and the reference electrode.
The diffusion is a function of the concentrations of
the species (e.g. ion species) on opposite sides of the
permeable barrier, and in its simplest fornn that is all
that is required of it, as it then functions only to
regulate the access of the sample or its components to the
detecting electrode. This regulation can be very helpful
in keeping the concentration of the components affecting
the detecting electrode potential within limits which allow
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ease of measurement or preventing excessive amounts
contacting the detecting electrode and distorting the
output signal or potential from it and consequently
distorting the accuracy of measurement.
The diffusion is usually inward diffusion (i.e.
through the permeable barrier from the sample towards the
detecting electrode) by the analyte species (e. g. ionic
species) to be determined. This results in the detecting
electrode being uniformly exposed to the inwardly diffusing
species to be measured. It also has the advantage that the
detecting electrode is less likely to be exposed to any
unsuitably high concentration of the analyte species before
the measurement is completed - as could be the case if the
sample contains a very high ionic concentration and an ISE
or redox electrode, as detecting electrode, were exposed
directly to the sample. In our present method, by the time
concentration levels within the permeable barrier rise
sufficiently to cause problems, the measurement usually can
have been completed.
Furthermore, it causes the concentration of the
analyte in contact with the detecting electrode to change
progressively as diffusion proceeds, and this change -
especially the rate of change of concentration - is an
exceptionally useful basis for the determination of analyte
(e.g. ion) content which we wish to make and a key
advantage provided in our present invention.
Alternatively, as a variant, the contents of the
permeable barrier may be provided with a concentration of
the analyte species (the analyte ion When the detector
electrode is an ISE) which is higher than that in the
sample to be examined, so that diffusion of the analyte
species will then be outwards - away from the detecting
electrode and into the sample - so resulting in a decrease
of its concentration adjacent to the detecting electrode.
This mode can also be used, as it is the rate of change
that can be. more important for the measurement purposes
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than the the absolute concentration itself or whether it is
increasing or decreasing - especially when using an ISE.
In the simplest form of our invention no selectivity
is necessary for the material of the permeable barrier but,
if desired, the permeable barrier may have selective
properties, especially in the way it limits ~#,usiOn.
This limitation of diffusion is distinct from selectivity
on the basis of other phenomena. This limitation of
diffusion is distinct from an ISE membrane selectivity
phenomenon. This could be important in improving the
apparent selectivity of a detecting electrode, especially a
redox electrode, and improved usefulness of our invention
may be secured by making the barrier of a material which
provides some degree of selectivity. This may then enable
the device to exclude any components which could compromise
the selective functioning of the detecting electrode, and
so serve as a means for eliminating problematic
interference with measurements being made. For this
variant, a complete or high degree of selectivity may not
be necessary, and even a partial discrimination against
access by particular components may be sufficient to ensure
satisfactorily reliable measurements - depending upon the
particular application of the invention and the nature of
the sample and/or the components sought to be determined.
It is usual for a zone of liquid (e . g . an electrolyte
medium) to be required between the detecting electrode and
the reference electrode within the permeable barrier, as a
~~filling,~~ though some forms of detecting electrode may be
able to function without the need for any such filling
electrolyte,
This electrolyte medium may be provided in a variety
of ways.
(1) It may be provided in the device as made. This allows
the device to be made in a form suitable for sale or
storage but also for immediate use. For this form, the
electrolyte can be in the form of a hydrated gel, which
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is both practicable and convenient.
(2) It may be added at the time it is to be used, for
example by making the device in a form in which the
detecting electrode (e.g. an ISB or redox electrode) is
surrounded by the permeable barrier material, and then
soaking it in a suitable liquid (e. g. electrolyte
solution) to make it ready for use. An example of this
mode is to use a thin permeable membrane (e.g. a
dialysis membrane) around the electrodes. Such a
membrane may comprise any conventional material, e.g.
cellulose or cellulosic material as often used for
dialysis membranes. If desired, the robustness of the
construction or the degree of permeability can be
obtained by using multiple layers of the membrane (which
may be the same or different). Using four layers of
dialysis membrane can provide a very convenient form of
such a device - though four is a number found to be
convenient, and not an obligatory one.
(3) It may be provided by obtaining the necessary liquid
from a sample itself, by permeation of water and
diffusion of any required electrolyte ions from the
sample through the barrier when the device and the
sample are brought together.
Our preference is for the last of these, (3) , but the
most readily practicable way we prefer is that marked (2)
above.
The permeable barrier is adapted to interface with a
sample under examination by the fact that at least the
detecting electrode - and preferably both the detecting
electrode and the reference electrode assembly - are
enclosed within the permeable barrier. This enables all
that is required of a sensor device to be included in a
single unit, by carrying the detecting electrode and the
reference electrode assembly upon a support which serves to
hold the assembly together while insulating the detecting
electrode and the reference electrode assembly from each
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other. Various forms of construction may employed. For
example, if the detecting electrode and the reference
electrode assembly are assembled upon a substantially flat
insulating support, the permeable barrier may take the form
of a "bubble" or ~~envelope" over them. This allows the
sample under study to be applied to the side of the
insulating support on which the electrodes are exposed, and
the electrical connections to the measuring circuit. The
electrical connecting leads to the electrodes will need to
be properly insulated, both chemically and electrically,
from the media around them so as to avoid any interference
of loss of the electrode signals.
Alternatively, the electrical connections to the two
electrodes can be made in the usual manner and all the
leads and connections from them insulated and sealed to
pass through the region within the permeable barrier. This
allows the whole device to be made in a form in which the
permeable barrier is more extensive and covers more than
just the area required for sample to be applied and access
the electrodes, so that the barrier can cover as much of
the device as desired - even the whole of it - so making it
easier to use by dipping into a sample.
The measuring circuit may be any of the conventional
ones for electrochemical measurement, and use conventional
apparatus (meters, recording devices, and the like) for
detecting an EMF or potential differences, and the signals
from the electrode system of our devices can be interpreted
and converted to specific measurements of components by
conventional methods.
When the detecting electrode is an ISE or redox
electrode, it may suffer interference from unknown amounts
of another species, e.g. ions or molecules. This
interference can be reduced or eliminated by filling the
enclosed region (around the detecting electrode and within
the permeable barrier) with a zone of liquid (e.g. an
electrolyte) containing an appropriately high concentration
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of this other species (especially an ion species) liable to
interfere with the desired measurements, so that it can
diffuse out through the permeable barrier and thereby
reduce interference from that species if present in the
sample. In this way, by "loading' the filling within the
permeable barrier, the concentration of the interfering
species can near the detecting electrode can be kept
substantially constant and its potentially troublesome
effects can be reduced - and especially it can be kept
effectively constant with time - so that measurements
showing the rate of change of yotential in the output
signal due to the desired analyte can thus be
distinguishable and used as the basis for determination of
analyte content.
The components of a sample which can be determined by
the use of an ISE according to the present invention are
those for which the conventional ion-selective electrodes
are applicable. These include anions, e.g. sodium (Na+)
and potassium (K+), and anions, e.g. nitrate (N03-) and
fluoride (F-) and chloride C1-, but others may be
determined if desired by appropriate ion-selective
electrodes. Selectivity can sometimes be improved by
appropriate choice of the barrier membrane. For example,
selectivity for organic anions (e.g. chloride C1-) may be
enhanced by use of an anionic barrier membrane.
The sample may be obtained and prepared in any
conventional manner, but is preferably a liquid. If solids
or samples which are not completely liquid are to examined,
it may be necessary to add water or other aqueous solvent
media to them to ensure that the components in them are put
into a suitable state for measurement.
Usually, all that is required is that the analyte
(e.g. ionic analyte) to be detected and measured should be
in solution in the sample so that it is able to diffuse
through the permeable barrier. The analyte may be present
initially in the sample under examination as such (and
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therefore can be determined directly), but if desired it
may be generated in situ, for example by enzyme or chemical
action (e.g. titration) and this may enable measurements of
some analytes to be made indirectly. Such indirect
measurement can be useful as means for making one analyte
into another which diffuses more readily through the
permeable barrier or be detected at the detecting electrode
(for example, when using an ISE, by converting a non-ionic
analyte into an ionic one), but it can also be used to
assist in reducing interference by components which could
otherwise behave similarly to the analyte that is to be
measured.
Redox measurements can also be made both directly and
indirectly, and may be made in these ways using our
invention. 8xamples of the latter are the "quinhydrone"
sensors for ph and potentiometric titration systems, and
other arrangements are possible. reagents or enzymes may
be added to the sample in any form or immobilised or
retailed above the covering permeable barrier (membrane) in
liquid or dry form, or dried in a gel or liquid layer below
it, for reaction above or below the permeable barrier
(membrane).
The sensor devices of this invention may be used in
substantially the same way as an ordinary detecting
electrode, by contacting the permeable barrier over the
detecting electrode with the sample (if, necessary,
prepared for this in the manner described above). This may
be done by applying it to the sensor device or, more
conveniently, by dipping the sensor device into the sample.
Of course, some forms of construction may be better adapted
for particular modes of contacting with the sample, but the
choice can easily be made to suit the particular situation
and the user's preferences.
In use, advantages which can be secured by use of an
ISE or redox electrode in the sensor devices of the present
invention include:
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(1) the ISE (or redox electrode) and the reference
electrode, being combined, make the device very much
more easy and convenient to use.
(2) potential problems of contamination of the reference
electrode are reduced or eliminated.
(3) the variety of analytes which can be measured is wide
because a considerable range of standard ion-selective
(e. g. ion-exchange) materials are available.
(4) selectivity of component measurement can be enhanced by
10 use of a perm-selective layer in the permeable barrier.
(5) small sample volumes can be examined and their contents
determined, particularly when using a flat form of
device.
(6) no calibration of the device is required to counteract
15 for any baseline drift. This is a key advantage so far
as practical use is concerned, as in "single shot" use.
(7) the device is simple enough to be made disposable, for
a "use once, no rinsing" procedure.
(8) in its flat form, the device is of a very similar
20 format to amperometric planar sensors, i.e. they can
use different circuitry but the same fabrication and
user presentation techniques, and so can offer
opportunities for "mixed technique" multi-analyte
sensor strips.
25 (9) adaptable to use any ISE system.
(10) advantageous for the examination of samples containing
the analyte at high concentrations which would not
allow the ISE to function satisfactorily if brought
into direct contact with the ISE.
30 Similar advantages - except of course those which are
peculiar to only an ISE - are found when using other types
of detecting electrode in place of an ISE, particularly a
redox electrode.
Applications for which the devices of the invention
35 may be used include medical and clinical use, especially as
a disposable sensor - which reduces risk of cross
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contamination between sample or subjects; checks on levels
of fertiliser components in soils, rivers, plant materials
and the like; checks on levels of components (Which may be
considered to be desirable ones or may be any considered as
5 contaminants or undesirable) in foods, waters, industrial
liquid and effluents and the like. This is especially
useful for the determination of ionic components or
contaminants, by use of an ISE.
The device is most advantageous for single use in a
10 constant sample, and after that use can be discarded.
After making a single measurement, i.e. not continuous
monitoring, the device can be "reconditioned" to some
extent so that it can be used again, but this can be slow
and not worthwhile. If it is to be re-used, the advantage
15 of calibration avoidance is effectively lost.
The devices of our invention may be made in a variety
of forms and shapes, to suit the particular needs of a
user. Thus, the device may be a single one - which can
then be made conveniently small and inexpensively, and be
20 most simple to use. Other forms include combinations or
arrays containing more than one of our sensor devices,
which may be constructed to obtain an enhanced output
signal for easier measurement or for special uses.
A form of interesting applicability is that in which
25 several individual sensor devices of our invention are
mounted together and the internal zone of liquid (e. g.
electrolyte) of each of these, within the permeable
barrier, is pre-loaded With different concentrations of the
analyte to be sought and measured. By contacting all the
30 sensor devices with the sample, the flux of any interfering
species (ions or molecules, or the like) will be be
constant for all of them, but the fluxes of the desired
analyte will be different and their differential behaviour
will then be a function of the concentration of the desired
35 analyte in the sample - and so enable interference effects
to be reduced or eliminated.
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Another variant of this is an array of a number of our
sensor devices, each with its own internal electrolyte
loaded with different pre-determined (and known)
concentrations of the analyte sought. When such an array
is contacted with the sample, the different sensors will
give different responsea - but for the particular sensor in
Which the loaded concentration of analyte (e. g. analyte
ion) equals that in the sample there will be no diffusion
through the permeable barrier and no potential change with
time will be observed. This can reduce the need for
detailed measurements to be made, as the sensor showing ~~no
change" ("nil diffusion") can be distinguished easily and
quickly and will indicate the analyte concentration
immediately. A measurement may be made by using signals of
more than one sensor element with appropriate signal
processing methods.
An especial feature in using our invention is in the
way in which the measurements are made and interpreted. As
exemplified by the use of an ISE, an ion to be determined
diffuses through the permeable barrier and this progressive
diffusion gives a continually changing response from the
ISE/reference electrode combination. We have found that,
using a sensor device of the present invention, the rate of
change of response is most useful as an indication of the
analyte content, and that it is possible to obtain more
reliable measures of the analyte concentration by
determining this. When measurements (by observation and
recording) of the output potential of the electrode system
are made, for example by being plotted, these show the rate
of change of potential and can be used as an indication or
measure of the analyte content. The slope of the output, as
measurements proceed and are thus plotted, is independent
if any baseline EMF and also of the particular reference
electrode used.
The responses are usually and conveniently measured in
mV/minute, and are plotted as the rate of change of
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potential against the concentration or, preferably, against
the log concentration. For this mode of using the
measurements, the absolute value of the ISE/reference or
redox/reference potential is not important so long as the
reference keeps stable during the short time reguired for
measurement, the problems previously caused by long term
drift are minimised, and the need for calibrations for use
are rendered substantially unnecessary. Though the
baseline EMF of ISE systems may drift about, this slope of
the response plot is much more stable. This is in contrast
to the usual way in which an ISE is used, which involves
waiting long enough for the ISE to be at equilibrium.
Similar effects are seen with redox systems.
Sometimes, during initial stages of setting up a
sensor device of our invention for use, it may be found
that there can be some initial abnormality (a "spike" or
surge) in the response, but this is only brief and can be
allowed to pass prior to making measurements to determine
the slope of the plot as indicated above.
The detailed description given herein, though written
with principal reference to an ISE as the detecting
electrode, should not be taken as meaning that the
invention is only applicable to the use of an ISE.
Emphasis has been put on an ISE because the invention is
seen as being especially suited to dealing with the
problems of using an ISE, but the description should be
read as being applicable to any other detecting electrode
which may be used in place of the ISE, particularly redox
electrodes.
The principle of operation of the invention lies in
the use of an enclosing permeable barrier to provide a zone
of liquid (usually an electrolyte) in contact with the
detecting electrode - and possibly with both the detecting
electrode and reference electrode - so that this zone of
liquid acts as an intermediate phase which can act to
moderate the extreme conditions which may which may be
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present in a sample under examination. The membrane
regulates the passage of components (e. g. ions) - whether
analyte components or not - between the sample and the zone
adjacent to the detecting electrode, in either direction.
This serves to improve the ability of the electrode system
(detector electrode and reference electrode) to cope with a
Wider variety of samples and give greater ease and accuracy
of measurement than is practicable when the electrode
system is exposed directly to the sample under examination.
More particularly, it enables rate measurements to be made
as detected species cross the permeable barrier (membrane)
and alter the concentration in the inner liquid region.
The invention is illustrated but not limited by the
following Example and accompanying drawings, which are
schematic and not drawn to scale.
EXAMPLE 1.
Figures 1 and 2 represent illustrations of forms of
sensor constructed according to the present invention, and
are schematic drawings, in transverse section and not to
scale.
In Figure 1, a planar sheet of ceramic material of
approximately 0.5 mm thickness and 1.5 cm by 3.0 cm in area
(1) serves as an insulating support and carries, upon one
of its planar surfaces, two electrodes -- (A) an ion
selective electrode comprising a thick metallic film (2) of
platinum deposited from a platinum-containing ink or paint
and coated with an ion-selective material (3), and (B) a
standard reference electrode (4) comprising a film of
silver coated with silver chloride, surrounded by an
aqueous solution (5) of potassium chloride (concentration
in the range 0.5 to 3.5 M) (5) and enclosed within a porous
layer (6) to serve as the required liquid junction in use.
The two electrodes (A) and (E) are totally enclosed by
a permeable barrier layer or membrane (8) which also makes
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sealing contact with the sheet of insulating support
material (1) all around the area containing both
electrodes. The space between this enclosing membrane (8)
and the two electrodes (A) and (B) is filled with an
aqueous solution (7) of sodium chloride. This completes
the electrolyte-filled permeable barrier as the enclosure
for the pair of electrodes.
On the other side of the planar support sheet (1),
remote from the two electrodes (A) and (8), electrical
leads are fitted (10 and 21 respectively) to provide
electrical connection to the electrodes (A) and (B) (more
specifically, to the conducting films (2) and (4) . These
leads (10 and Z1) are sealed into the sheet (1) to prevent
leakage of liquid past them, and are insulated and provided
with means for connection to a voltage measuring device V
(not shown).
In use, a liquid sample to be examined (9) is put into
contact with the surrounding membrane (8). Conveniently,
this is done by simple dipping the assembly (constructed as
described above) into the sample liquid (9). The
insulation covering on the connecting leads (10 and 11)
ensures that there is no electrical short-circuit occurring
between them. Alternatively, the assembly is laid
horizontally, with the electrodes, membranes, etc.
uppermost, and the sample is then applied on top of the
outer membrane (8).
This construction allows electrolyte contact at each
of the membranes (3) and (8) and also the bridging part
(7), to allow the completion of an electrically conducting
circuit between electrode (A) and (B), which avoids direct
exposure of electrode coverings (3( and (6) to the sample
( 9 ) itself .
Measurement of the potential between the two
electrodes (A) and (B) is made by an appropriate meter,
usually an IS8 meter, typically a voltmeter With a single
high impedance input for the ISE.
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In Figure 2, which represents a transverse section of
part of a long strip of a ceramic base (1) coated with a
pair of metallic stripes (12) and (13). Stripe (12) is of
gold and serves as a conductor for the ISE part, and stripe
(3) is of metallic silver coated with silver chloride and
serves as the reference electrode. Over the base (11) is a
layer of insulating material (14), made by casting a
solution of un-plasticised PVC in tetrahydrofuran over the
stripe-coated ceramic base and allowing the solvent to
evaporate off. A small "window" in the deposit of PVC is
left so that the stripes (12) and (13) are exposed and not
covered by the PVC (14). Then, the area over and around
the gold stripe (12) is coated with a solution of PVC, a
plasticiser, and an ion-carrier to form a coating (15).
Then finally the whole area which is not covered by the PVC
(14) is covered with polyvinyl alcohol, which forms a
permeable layer (16) which is sealed on to the surrounding
PVC (14) and completely covers the electrodes. Electrical
connections are made (by means not shown, but conveniently
comprising the ends of stripes (12) and (13) protruding
from under the PVC layer (14) beyond the "well" or "window"
filled by the layers (15) and (16). For use, the sample is
then contacted with the of the polyvinyl alcohol layer
(16), and the potential difference between electrodes (12)
and (13) is measured.
In this fozm of construction, basically electrolyte
and membrane are combined.
For these electrodes, the un-plasticised PVC used has
a molecular weight of 100,000 to 200,000 and is dissolved
in tetrahydrofuran. This is used to form the PVC layers.
To make the IS8 coatings (3) and (15), the solution of
un-plasticised PVC in tetrahydrofuran is used, with
addition of tri-caprylyl methyl ammonium chloride as
plasticiser and as ion carrier for chloride or with di-
octyl phthalate as plasticiser and valinomycin as ion-
carrier for potassium.
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The layers of metal are deposited from metal-
containing paints, in conventional manner, and the various
coatings of polymer-based material are applied by dip-
coating the ceramic strip in the solutions, masking areas
which are not to be coated and cutting out parts of the
applied coatings where a "well" or "window" is to be
formed.
In place of the gold, using platinum and copper as
alternative metals gives substantially the same results.
Comparable results are also obtained by direct or
indirect use of a redox electrode system instead of an ISE.
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